On September 15, 2016 the Australian Government Response to the Review of Medicines and Medical Devices Regulation was released. It identifies ways to improve access to therapeutic goods for consumers and remove unnecessary red-tape for industry while maintaining the safety of therapeutic goods in Australia.
The report of the Expert Panel Review, which was set up by the Commonwealth Department of Health in October 2014, notes the increasing globalisation of the pharmaceutical and medical devices industries and the rapid pace of innovation, and accordingly made recommendations as to how to position the Therapeutic Goods Administration (TGA) to respond to these trends in the future.
In fact, most of the report, and therefore the Government response, refers to this growing internationalisation, and thus looks predominantly at how to carry overseas approvals into the Australia market, cutting down on unnecessary duplication of effort.
The Review report made recommendations that were “significant in scale and scope”.
Accordingly, the Government response says, the Department of Health conducted a number of consultations on particular recommendations, as part of a consultative and collaborative approach to reform. “The consultations were central to the formulation of this response.”
“This response presents a strategic and systems-based approach to achieve long-term sustainable reform to the regulation of therapeutic goods in Australia. It identifies ways to improve access to therapeutic goods for consumers and remove unnecessary red tape for industry whilst maintaining the safety of therapeutic goods in Australia.”
References to particular medical procedures and practices, and particularly to complementary medicine, fall toward the end of the report. At one stage the report says that “the regulation of complementary medicines will be reformed to provide new pathways where evidence of efficacy will be reviewed by the TGA prior to market and compliance powers strengthened, whilst recognising the low-risk nature of complementary medicines”.
It has been noted in the past that the TGA lacks resources in assessing the broad range of products listed on the Australian Register of Therapeutic Goods (ARTG), leading it to concentrate on what it deems ‘high risk’ products rather than look at levels of efficacy of those products. It has also been highlighted that the TGA lacks regulatory power in dealing with infractions, rather offering rulings that have been shown to be easily circumvented by suppliers, simply through repackaging products that retain their existing formulations.
Despite this, the Review “recognised that the TGA has an excellent reputation internationally and domestically for its role in ensuring the timely availability of safe, efficacious and high quality therapeutic goods”.
Activist Dr Ken Harvey told Pharmacy News that “The worst offenders of misleading and deceptive claims are not members of industry associations, so self-regulation offered by industry associations will not pick these up. The horses will bolt!”
He gave guarded support for some principles in the review but emphasised that “the devil is in the detail”, with special concerns around soft levels of severity and lack of timeliness of penalties for breaking the rules.
“We are currently running at 80 per cent regulatory non-compliance with TGA post-marketing reviews and 98 per cent upheld complaints by the TGACRP. In short, there is money to be made in breaking the rules!”
Following the review and the Government response, the TGA says that it will develop a searchable catalogue of approved ingredients for use in listed medicines that can be accessed on the TGA website by sponsors, healthcare professionals and consumers.
“We will also develop a list of ‘Permitted Indications’ which sponsors must use to describe the permitted therapeutic uses for listed complementary medicines. In doing so, ‘free text’ will no longer be allowed when listing these products on the ARTG. Together, these proposals will reduce administrative costs for industry and protect consumers from potentially misleading therapeutic claims.
“Criteria will need to be developed for identifying those overseas regulators we can work-share with, and those with assessments which can be used for this purpose.”
The TGA says that “a new class of complementary medicines will be introduced”.
The TGA promises that “Evidence for efficacy alone for these products will be evaluated by TGA prior to their market authorisation. Sponsors of these medicines will be able to make therapeutic claims, supported by the evidence, that go beyond those available for listed medicines but of a lower level than those allowed for registered medicines. Criteria for these medicines will be developed in consultation with sponsors, consumers and health care professionals.”
For complementary medicines that have been assessed for efficacy alone as part of the pre-market authorisation process, sponsors will be able to use promotional material to indicate that a product has been assessed as efficacious. “Implementation of this change will improve the evidence base of the sector and encourage innovation,” the TGA says.
The reforms will be progressively rolled out by the TGA over the next 18 to 24 months, with new regulatory pathways for some medicines in place within 12 months.
Changes in summary
The TGA says that changes being made to regulation of complementary medicines will:
• Provide consolidated lists of permitted ingredients and permitted indications;
• Make greater use of assessments for ingredients and products by comparable overseas regulators;
• Implement an additional approval pathways for new complementary medicines which include pre-market assessment by TGA of evidence for efficacy for listed medicines;
• Improve transparency for both industry and consumers by establishing a catalogue of approved ingredients and a list of permitted indications for use in complementary medicine;
• Introduce statutory timeframes for the approval of new ingredients;
• Adopt a risk-based approach to the variation of complementary medicines.
Existing pathways which enable listing of a complementary medicine through sponsor self-declaration and registration of a complementary medicine through full TGA pre-market assessment will continue.
The TGA says that these reforms will:
• Support consumer health decisions by increasing the information available on the efficacy of complementary medicines; and
• Increase certainty of processes and increase flexibility for industry.
Complementary medicines sponsors will decide which pathway they wish to follow.
Relevant recommendations and response
The following are the Review’s recommendations and Government responses where they refer to complementary medicines. The full list of recommendations can be found here.
The Panel recommends that listed medicinal products, including complementary medicinal products, and the ingredients for use in such products, continue to be regulated within the therapeutic goods framework.
The Commonwealth response: The Commonwealth accepts Recommendation Thirty-Three, noting the strong support from all stakeholders for complementary medicines to continue to be regulated by the TGA.
The Panel recommends that the redrafted Therapeutic Goods Act 1989 is amended to provide the Australian National Regulatory Authority (NRA) with the capacity to refuse to list in the ARTG complementary medicinal products and other listed medicinal products that have the potential to undermine Australia’s public health efforts.
Response: The Commonwealth supports the intent of Recommendation Thirty-Four, noting that current mechanisms (such as allowing complementary medicines to contain only ingredients that have been assessed by the TGA to be safe, and targeted reviews of particular types of products immediately post-listing) can achieve the intent of the recommendation.
The Panel recommends that the NRA continues to evaluate ingredients for use in listed medicinal products, and requires listed medicinal products to only include ingredients that have been approved for use in listed products. In undertaking an evaluation of ingredients the NRA should continue to give consideration to:
A. The safety of the proposed ingredient, taking into account factors such as: proposed dosage; route of administration; frequency and duration of administration; and possible drug interactions;
B. Working with stakeholders to identify a broader range of appropriate sources of evidence for the quality of new ingredients, which may change over time; and
C. The quality of the proposed ingredients, including proposed methodology for ensuring product purity, consistency, stability and other aspects of the PIC/S GMP.
Response: The Commonwealth accepts Recommendation Thirty-Five, noting that stakeholders were in favour of the TGA continuing to evaluate ingredients for use in listed medicinal products.
The Panel recommends that a sponsor seeking to have a new ingredient assessed by the NRA for use in listed medicinal products, including complementary medicinal products, is able to either:
A. Submit data relating to the safety and quality of the proposed ingredient for use in listed medicinal products for de novo assessment by the NRA; or
B. Submit an un-redacted evaluation report from a comparable overseas NRA, along with a copy of the dossier submitted to that NRA and data supporting specific Australian requirements, such as labelling, to the Australian NRA for assessment (refer to Recommendation Five). The Australian NRA to make a recommendation regarding use of the ingredient in listed medicinal products once it has considered the data within the Australian context.
Response: The Commonwealth accepts Recommendation Thirty-Six, as it will provide additional flexibility for applicants looking to apply for assessment of new ingredients for use in listed medicines. The Commonwealth notes that take-up of Option B will depend on the availability of relevant un-redacted evaluation reports from comparable overseas regulatory agencies.
The Panel recommends that the NRA develop and maintain, in real time, a catalogue of approved ingredients for use in listed medicinal products that is readily accessible to sponsors and the general public.
Response: The Commonwealth accepts Recommendation Thirty-Seven, as it will provide a single readily accessible list of ingredients for sponsors and the general public, minimising unnecessary regulatory burden.
The Panel recommends that the NRA establishes the list of Permitted Indications, from which sponsors must exclusively draw, for listed medicinal products in the ARTG.
Response: The Commonwealth accepts Recommendation Thirty-Eight, noting that implementation of the list of Permitted Indications will require legislative change and will be subject to consultation with consumers, sponsors and health professionals.
The Panel recommends that there be three options by which sponsors may seek entry into the ARTG of complementary medicinal products and other listed medicinal products for supply in Australia.
Listing in the ARTG following self-declaration by the sponsor of the safety and quality of the product in circumstances where:
A. The product contains only ingredients that have been previously approved by the NRA for inclusion in listed medicinal products; and
B. The ingredients, including proposed dosage where applicable, route of administration, and duration of use where applicable, comply with listing notices or similar documents issued or endorsed by the NRA; and
C. the ingredients comply with any compositional guidelines or other compendial standards issued, adopted or approved by the NRA; and
D. The product is manufactured in accordance with PIC/S GMP; and
E. The sponsor only seeks to make claims regarding the indications for use of the product selected from the list of Permitted Indications (Recommendation Thirty Eight refers); and
F. The sponsor holds evidence to support these indications, consistent with requirements outlined in the evidence guidelines issued by the NRA from time to time.
Listing in the ARTG following a self-assessment of the safety and quality of the product, and following assessment of the efficacy of the product by the NRA, in circumstances where:
A. The product contains only ingredients that have been previously approved by the NRA for inclusion in listed medicinal products; and
B. The ingredients, including proposed dosage where applicable, route of administration, and duration of use where applicable, are compliant with listing notices or similar documents issued or endorsed by the NRA; and
C. The ingredients comply with any compositional guidelines or other compendial standards issued, adopted or approved by the NRA; and
D. The product is manufactured in accordance with PIC/S GMP; and
E. The sponsor seeks to make health claims that fall outside the list of Permitted Indications but which are still appropriate for listed medicinal products; and
F. The sponsor can provide evidence acceptable to the NRA to support the safety and efficacy of the product for the proposed indication(s), commensurate with risk. This may include the submission of an un-redacted evaluation report(s) from a comparable overseas regulator.
Registration of a complementary medicinal product in the ARTG following an assessment by the NRA of the product for safety, quality and efficacy in accordance with existing requirements for registration of complementary medicines (Recommendation Forty refers).
The Commonwealth’s Response: The Commonwealth accepts Recommendation Thirty-Nine, noting that legislative amendments are required to implement Option Two. Implementing this recommendation would increase transparency for consumers, provide additional flexibility for sponsors and support innovation.
The Panel recommends that where a sponsor seeks to include a complementary medicinal product in the ARTG that the sponsor is able to do so utilising registration Pathways One or Two, namely:
Pathway One – Submission of a complete dossier for de novo assessment.
This assessment may be undertaken in full by the Australian NRA or via a work-sharing arrangement between the Australian NRA and a comparable overseas NRA.
Pathway Two – Submission of an un-redacted evaluation report from a comparable overseas NRA, along with a copy of the dossier submitted to the comparable overseas NRA and Australian specific data similar to that provided by sponsors in Module 1 of the Common Technical Document, for assessment by the Australian NRA. The Australian NRA to make a recommendation regarding registration of the complementary medicinal product once it has considered the data within the Australian context
Response: The Commonwealth accepts Recommendation Forty, as it will increase flexibility for sponsors seeking to register a complementary medicine in the ARTG. This recommendation is consistent with the Australian Government’s Regulatory Reform Agenda and the Industry Innovation and Competitiveness Agenda
The Panel recommends that the NRA develops, in consultation with industry, legislative timeframes for the:
A. Assessment of new ingredients for use in listed medicinal products;
B. Publication of finalised compositional guidelines for newly approved
ingredients for use in listed medicinal products, where appropriate;
C. Assessment of medicinal products listed under Option Two; and
D. Registration of medicinal products under Option Three.
Response: The Commonwealth accepts Recommendation Forty-One, noting that development of legislative timeframes will be subject to further consultation with stakeholders.
The Panel recommends that, consistent with Recommendation Thirteen, the NRA adopt a risk-based approach to the management of variations to complementary medicines listed in the ARTG.
This approach should provide for:
A. notification of variations to the NRA in circumstances where the variation does not impact the quality, safety or efficacy of the product; or
B. assessment of the variation by the NRA in circumstances where the variation has the potential to impact the safety, quality or efficacy of the medicine. This assessment to be abridged in scope, so that only those aspects that require evaluation in order to establish the continued safety, quality and efficacy of the complementary medicine following implementation of the proposed variation are examined (abridged assessment).
Response: The Commonwealth accepts Recommendation Forty-Two. Implementing a risk-based approach to assessments of variations to listed complementary medicines will reduce regulatory burden for sponsors.
The Panel recommends that where a medicinal product is listed in the ARTG, the sponsor be required to publish on the sponsor’s website or, if the sponsor does not have a website, on another website nominated by the NRA, the evidence that it holds to support all indications included in the ARTG entry.
Response: The Commonwealth supports the intent of Recommendation Forty-Three, which is to better inform consumers and improve the accuracy of information available to them. Consistent with the principles of minimum effective regulation, the Commonwealth will encourage self-publishing by sponsors of relevant information.
The Panel recommends that where a medicinal product is listed in the ARTG under Option One (self-assessment), the sponsor is required to include a prominent disclaimer on all promotional materials relating to the product, including product information on websites, to the effect that the efficacy claims for the product have not been independently assessed and/or are based on traditional use.
Response: The Commonwealth supports the intent of Recommendation Forty-Four, which is to assist in educating consumers about the listing system. Noting that careful design and consultation with affected stakeholders would be required prior to any implementation, the TGA will conduct further consultation on ways to better educate consumers about the listing system, including consideration of an educative statement about the difference between listed and registered medicines to be placed on sponsors’ websites. In accordance with the Government’s commitment to red tape reduction, the Government will not require sponsors to place a disclaimer on product labels.
The Panel recommends that where a medicinal product is listed in the ARTG following an assessment by the NRA of an application under Option Two, the sponsor is able to indicate on all promotional materials and on the product label, that the efficacy of the product has been independently assessed for the approved indication(s).
Response: The Commonwealth accepts – in principle – Recommendation
Forty-Five, noting that the design and use of the promotional statements will require careful consideration by the TGA and further consultation with stakeholders.
The Panel recommends that the NRA develops or adopts from comparable overseas regulators, efficacy monographs for commonly used active ingredients that have been approved for use in listed medicinal products. Such monographs would document the evidence supporting the efficacy of the ingredients for specific indications and other relevant information.
Response: The Commonwealth accepts Recommendation Forty-Six, as the development or adoption from comparable regulators of monographs has the potential to improve the availability and accuracy of information for consumers and to reduce time and costs for industry.
The Panel recommends that, in revising the Therapeutic Goods Act 1989 and subordinate legislation (Recommendation Twenty Eight refers), the Australian
Government provides review and appeal rights for the sponsor who has lodged an application for a new ingredient (to be approved for a listed medicine) to seek a review of an NRA decision regarding that application.
Response: The Commonwealth supports the intent of Recommendation Forty-Seven. The design of potential review and appeal rights requires careful consideration of the application of administrative law principles in this context.
The Panel recommends that the Australian Government undertakes a review of the range of complementary medicinal products, currently listed in the ARTG and subject to regulation under the medicines framework, with a view to ensuring that products that might best be regulated under other regulatory frameworks, without undermining public health and safety, are removed from the auspices of the Act.
Response: The Commonwealth accepts Recommendation Forty-Eight, noting that the review will involve consultation with consumers, industry, health professionals and other Commonwealth regulatory bodies. Implementation of this recommendation will be furthered in conjunction with that of Recommendations Fourteen and Twenty-Three.
The Panel recommends that the NRA develops a more comprehensive post-market monitoring scheme for listed medicinal products, including complementary medicinal products.
Such a scheme should include:
A. An increase in the number of products subject to random/targeted post-market review;
B. Provisions to allow the NRA to complete a post-market review in the event that the sponsor withdraws the product from the ARTG during the course of the review;
C. Timely availability of information for consumers for each listed product in relation to whether the product has been subject to post-market review, and the timing and outcome of any review;
D. Integration and timely analysis of any available datasets, including eHealth and hospital records, to provide a more streamlined and cost-effective approach to post-market monitoring (Recommendation Twenty-Seven refers), particularly of products including newly approved ingredients;
E. Provision for electronic reporting of adverse events; and
F. Enhanced collaboration with overseas NRAs to share information relating to safety or efficacy of comparable products.
Response: The Commonwealth accepts Recommendation Forty-Nine, as the development of a more comprehensive post-market monitoring scheme will enhance consumer protection and complement existing post-market monitoring processes. With respect to parts B and C of Recommendation Forty-Nine, the Commonwealth notes that the intent of these parts is already achieved through use of existing mechanisms available to the regulator such as targeted post-market audits.
The Panel recommends that the Australian Government gives consideration to improving the competitiveness of the Australian complementary medicines industry by providing incentives for innovation.
Response: The Commonwealth accepts – in principle – Recommendation Fifty, noting the cross government responsibility for innovation policy. The Department of Health will collaborate with other Departments (such as the Department of Industry, Innovation and Science) and with relevant stakeholders to consider this issue further. This reform aligns with the Australian Government’s National Innovation and Science Agenda.
The Panel recommends that the statutory Advisory Committee on Complementary Medicines is retained, and that the committee:
A. Is composed of a range of experts across relevant fields and consumer representation, as required over time;
B. At the request of the NRA, provides advice regarding the inclusion, variation, removal of complementary medicinal products from the ARTG and any other matters relating to complementary medicines; and
C. Takes into account any other information that the committee considers is material to its deliberations.
Response: The Commonwealth accepts Recommendation Fifty-One. The Advisory Committee on Complementary Medicines will provide an important opportunity for TGA to receive expert advice from consumers, industry and health professionals in the complementary medicines sector.
[Recommendations 52-54 concern the promotion of general therapeutic products.]
The Panel recommends that the whole process of vetting and pre-approval of the advertising of therapeutic products to the public is stopped in favour of a more self-regulatory regime.
Response: The Commonwealth accepts Recommendation Fifty-Five, noting that the acceptance of Recommendations Fifty-Seven (enforcement powers) and Fifty-Eight (sponsor education) is critical for managing potential concerns by consumers and healthcare professionals in accepting this recommendation. Removal of pre-approval requirements could help reduce unnecessary complexity for sponsors and advertisers, and is consistent with the Government’s commitment to minimising unnecessary regulatory burden.
The Panel recommends that current mechanisms for managing complaints are disbanded and a new mechanism is established consistent with best practice principles for complaint handling. In establishing the new complaints management mechanism, a single agency should be responsible to receive and manage complaints on the advertising of therapeutic products to the public. The Government should consider the following options:
A. Establishing the function within the NRA or other existing Commonwealth agency and ensuring appropriate resourcing for the function; or
B. Calling for tenders from external organisations to undertake the function.
Response: The Commonwealth accepts Recommendation Fifty-Six. A single agency approach to complaints management has the potential to reduce complexity and encourage greater consistency in decision-making, benefiting consumers. To progress this recommendation, the Department of Health will consult with stakeholders on the appropriate design of the new complaints-management process.
The Panel recommends that, further to Recommendation Twenty-Eight regarding a review of the Act, consideration be given as to whether the current range of investigation and enforcement powers should be broadened.
Response: The Commonwealth accepts Recommendation Fifty-Seven, and notes that broadening enforcement powers will benefit consumers by appropriate compliance with advertising regulatory requirements, and deter inappropriate and misleading advertising of products.
The Panel recommends that the NRA facilitates the development of a formal sponsor education programme to provide industry and industry associations with appropriate information and tools to assist them in achieving compliance with advertising requirements under the regulatory framework.
Response: The Commonwealth accepts Recommendation Fifty-Eight, as developing sponsor education programmes to assist sponsors and advertisers in understanding their obligations will be particularly important once the reforms to the advertising regulatory framework are in place (particularly implementation of Recommendation Fifty-Five).